Familial hypercholesterolaemia is one of the most common dominantly inherited disorders to be identified in primary care, leading to raised serum cholesterol evident from the first year of life. Around 1 in 500 people are affected by this condition, but less than 15% of these are currently attending lipid clinics, suggesting that the vast majority are unrecognised in general practice. The recently released National Institute for Health and Clinical Excellence evidencebased guideline on the identification and management of familial hypercholesterolaemia provides an opportunity to bridge this gap. Primary care has a role in systematic and opportunistic case finding, such as recognising the relevance of a family history of premature coronary heart disease and/or grossly elevated cholesterol. Although affected individuals need specialist care, GPs can reinforce the information provided by specialists and support cascade screening to other affected members of the extended family.

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BackgroundIn vitro fertilization (IVF) patients receive various adjuvant therapies to enhance success rates, but the true benefit is actively debated. Growth hormone (GH) and dehydroepiandrosterone (DHEA) supplementation were assessed in women undergoing fresh IVF transfer cycles and categorized as poor prognosis from five criteria.MethodsData were retrospectively analyzed from 626 women undergoing 626 IVF cycles, where they received no adjuvant, GH alone, or GH–DHEA in combination. A small group received DHEA alone. The utilization of adjuvants was decided between the attending clinician and the patient depending on various factors including cost.ResultsDespite patients being significantly older with lower ovarian reserve, live birth rates were significantly greater with GH alone (18.6%) and with GH-DHEA (13.0%) in comparison to those with no adjuvant (p < 0.003). No significant difference was observed between the GH groups (p = 0.181). Overall, patient age, quality of the transferred embryo, and GH treatment were the only significant independent predictors of live birth chance. Following adjustment for patient age, antral follicle count, and quality of transferred embryo, GH alone and GH–DHEA led to a 7.1-fold and 5.6-fold increase in live birth chance, respectively (p < 0.000).ConclusionThese data indicated that GH adjuvant may support more live births, particularly in younger women, and importantly, the positive effects of GH treatment were still observed even if DHEA was also used in combination. However, supplementation with DHEA did not indicate any potentiating benefit or modify the effects of GH treatment. Due to the retrospective design, and the risk of a selection bias, caution is advised in the interpretation of the data.

IntroductionThe development of the concept and practice of business process re-engineering from the "Management in the 1990s" research programme at MIT[1], Hammer's well-known initial article on re-engineering in Harvard Business Review [2] and Davenport's book on process innovation[3], was at first sight highly biased towards the exploitation of IT. However, it was clear that many of the examples given of BPR had a very strong operations management and services management content. Some authors on BPR do, of course, already acknowledge antecedents in manufacturing, logistics and supply chain concepts [4]. The purpose of this article is not to claim BPR as an operations management approach but to examine the concepts and techniques of the field which might have application for BPR. Hence the learning which has been gained from other improvement philosophies may be valuably transferred to BPR programmes.Our starting point for this examination is the following description of BPR:An organisation may be considered as a collection of processes characterised as strategic, operational and enabling. BPR is an approach to achieving radical improvements in performance by using resources in ways which maximise value added activities and minimise activities which only add cost -either at the level of the individual process or at the level of the whole organisation.Implicit in this definition of BPR is the consideration of organizational structure. If an organization is viewed as a collection of processes how do the processes impact on a functional view of the organization? The debate about the relative importance of processes over functions where processes cross traditional functional boundaries is likely to be a feature of implementation of BPR [5]. The rules of BPRAs a prescription or framework for how to undertake BPR we have combined the principles of re-engineering proposed by Hammer[2] and the characteristics

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This retrospective study examines the influence of recombinant growth hormone (rGH) and melatonin adjuvants on oocyte numbers, embryo utilization and live births arising from 3637 autologous IVF±ICSI treatment cycles undertaken on 2376 women across ten years (2011-2020) within a pioneer Australian facility. Despite using an FSH-dosing algorithm enabling maximal doses up to 450 IU for women with reduced ovarian reserve, younger women had significantly higher mean numbers of oocytes recovered than older women ranging from 11.1 for women <35 years to 9.4 for women aged 35-39 years reducing to 6.5 for women aged 40-44 years and 4.0 for those aged ≥45 years (p<0.0001). Overall, the embryo utilization rate was 48.5% and live birth productivity rate was 35.4 % across all ages and neither rGH nor melatonin showed any benefit on these rates, in fact, those women with nil adjuvants showed the highest live birth rate per initiated cycle (42.0% overall: p<0.0001, and 55.3% for the youngest group: p<0.001). Embryo utilization was increased marginally by rGH in those women aged 40-44 years who had high ovarian reserve (p<0.05), but this benefit did not translate into any improvement in the live birth rate. Similarly, other factors known to cause a poor prognosis, including low IGF-1 profile, recurrent implantation failure, and low oocyte numbers at OPU, showed no improvement in embryo utilization nor in live births from the adjuvants. The relevance of embryo quality was examined on 1135 women whose residual embryos after a single fresh-embryo transfer failed to develop to a suitable grade for cryopreservation. From 1727 cycles such women often displayed an improved embryo utilization rate with rGH, but not with melatonin. Even so, live birth rates were not improved by either of the adjuvants.

This retrospective study examines the influence of recombinant growth hormone (rGH) and dehydroepiandrosterone (DHEA) adjuvants on oocyte numbers, embryo utilization and live births arising from 3637 autologous IVF±ICSI treatment cycles undertaken on 2376 women across ten years (2011-2020) within a pioneer Australian facility. Despite using an FSH-dosing algorithm enabling maximal doses up to 450 IU for women with reduced ovarian reserve, younger women had significantly higher mean numbers of oocytes recovered than older women ranging from 11.1 for women <35 years to 9.4 for women aged 35-39 years reducing to 6.5 for women aged 40-44 years and 4.1 for those aged ≥45 years (p<0.0001). Overall, the embryo utilization rate was 48.5% and live birth productivity rate was 35.4 % across all ages and neither rGH nor DHEA showed any benefit on these rates, in fact, those women with nil adjuvants showed the highest live birth rate per initiated cycle (44.94% overall: p<0.0001, and 55.2% for the youngest group: p<0.001). Embryo utilization was increased by rGH in those women aged 40-44 years who had low ovarian reserve (p<0.0001), but this benefit did not translate into any improvement in the live birth rate, in fact those women who did not use adjuvants had the highest overall birth rate (p<0.0001). Similarly, other factors known to cause a poor prognosis, including low IGF-1 profile, recurrent implantation failure, and low oocyte numbers at OPU, showed no improvement in embryo utilization nor in live births from the adjuvants. The relevance of embryo quality was examined on 1135 women whose residual embryos after a single fresh-embryo transfer failed to develop to a suitable grade for cryopreservation. From 1727 cycles such women often displayed an improved embryo utilization rate with both rGH, and with DHEA or combined rGH+DHEA. Even so, live birth rates were not improved by either of the adjuvants excepting young women <35 years using rGH without DHEA (p<0.05). Examining poor prognosis sub-groups, indicated both rGH and DHEA or combined rGH+DHEA consistently improved embryo utilization in those women with low ovarian reserve (p<0.0001), or those with low IGF-1 levels (p<0.0001) or with recurrent implantation failure (p<0.02). All the poor-prognosis sub-groups showed low live birth rates and, notwithstanding the improvements in embryo utilization, the live birth rates were not significantly improved by the adjuvants, albeit the rates were closer to the nil adjuvant groups (not significantly different).

Following 5 recent studies at PIVET several female factors were defined which enabled the clear categorization for a poor prognosis in IVF, namely advanced female age ≥42 years, very low antral follicle count (AFC <5), very low serum anti-Mullerian hormone level (AMH<5pmol/L), serum Insulin growth factor-1 (IGF-1 level) in the lowest quartile, repetitive failed IVF cycles (≥3) and the failure of residual embryos to undergo cryopreservation. Following an Assessment Cycle (AC) to define the first 4 factors in IVF-naïve women, women were offered recombinant growth hormone (rGH) as an adjuvant at 1.0 IU daily for 6 weeks in the lead-up to the oocyte pick-up of their first IVF treatment cycle. Of 1173 women who proceeded directly into IVF after completing an AC, 252 women (21.5%) utilized rGH initiating 426 IVF cycles. Very low AFC and AMH levels were defined in 51 of the women who proceeded through 90 IVF treatment cycles utilizing rGH. Clinical outcomes included cancellation rates (reduced among rGH users, p<0.01), oocytes retrieved (no significant benefit from rGH), oocyte utilization (apparent benefit for rGH in older women with several factors), significant improvement in embryo utilization rates for older women with several factors (incremental cycles ≥3; p<0.002) or failure to achieve cryopreserved embryos (p<0.02). However, these benefits failed to translate into an improved pregnancy or live birth productivity rate nor a reduction in miscarriage rates; partly due to the low numbers of women with several poor prognosis factors. Furthermore, a note of caution emerged from this study as younger women who did not receive rGH had significantly better live birth outcomes (p<0.0001 from initiated cycles), regardless of the number of poor prognosis factors identified. Nonetheless, we encourage prospective studies to continue, focusing only on older women ≥40 years with low ovarian reserve and additional poor prognosis factors.